The field of the invention is the treatment of neurological diseases and stress-induced conditions, including developmental neurological disorder and mood disorders.
Early life stress and trauma is a prominent risk factor for several psychiatric illnesses, including mood and anxiety disorders (Holmes et al., 2005). Further, in utero maternal stress has been shown in clinical studies (pregnant women's exposure to a range of traumatic, as well as chronic and common life stressors (i.e., bereavement, daily hassles, and earthquake)) to result in significant alterations in children's neurodevelopment, including increased risk for mixed handedness, autism, affective disorders, and reduced cognitive ability. (Talge N M, Neal C, Glover V. Antenatal maternal stress and long-term effects on child neurodevelopment: how and why? J Child Psychol Psychiatry. 2007; 48(3-4):245-61). More recently, maternal antenatal anxiety and/or depression have been shown to predict increased risk for neurodevelopmental disorders in children, and to confer risk for future mental illness. (O'Connor et al., Maternal antenatal anxiety and behavioural/emotional problems in children: a test of a programming hypothesis, Child Psychol Psychiatry. 2003 October; 44(7):1025-36). While early-life stress effects and in utero effects on adult psychopathology may depend upon genetic risk, the nature of gene and environment interaction is thought to play a role in the outcome.
Mood disorders are presently treated by a number of antidepressant medications. Most of these drugs are either tricyclic antidepressants (TCAs) or selective serotonin re-uptake inhibitors (SSRIs). The efficacy of these drugs differs substantially among patients. These therapies can also have significant side effects. For example, more than a third of patients taking SSRIs experience sexual dysfunction. Other problematic side effects include gastrointestinal disturbances, often manifested as nausea and occasional vomiting, agitation, insomnia, weight gain, and onset of diabetes.
Present drugs directly bind serotonin receptors to affect neuronal activity, affecting all neurons expressing serotonin receptors to increase the levels of serotonin in the central nervous system (CNS).
Therefore, there is need for additional treatment options for mood disorders by targeting novel pathways that can directly affect serotonin receptor expression in subsets of neuronal populations. The present invention is directed to meeting this and other needs.